Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status
Claims 1-20 are pending and under examination.
Priority
This application is a continuation application of U.S. Application Serial No. 19/176,900, filed April 11, 2025, which is a divisional application of U.S. Application Serial No. 17/696,267, filed March 16, 2022, which is a continuation application of U.S. Application Serial No. 16/163,055, filed October 17, 2018.
Information Disclosure Statement
The Information Disclosure Statement filed 9/22/2025 has been considered by the Examiner. The submission is in compliance with the provisions of 37 CFR §§ 1.97 and 1.98. Enclosed with this Office Action is a return-copy of the Forms PTO-1449 with the Examiner’s signature and indication of those references that have been considered.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
A. Claims 1-5, 10, 11, 18, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Horowitz et al. (US 2004/0157802 A1 – cited in 9/22/2025 IDS) in view of Kuramata et al. (Environ. Chem. 2016, 13, 723–731 – cited in 9/22/2025 IDS).
Claimed invention
Claim 1 is drawn to a method of killing or inhibiting the growth of an infectious agent other than Escherichia coli, comprising contacting the infectious agent with an effective amount of arsinothricin or a salt thereof.
Claim 11 is drawn to a method of treating an infection in a subject caused by an infectious agent other than Escherichia coli, comprising administering to the subject arsinothricin or a salt thereof at an effective dose in the range of from about 0.001 to about 100 mg/kg of body weight per day.
Prior art
Horowitz teaches novel antimicrobial compositions containing analogues of L-methionine-SR-sulfoximine (MSO) having general formula 1
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. See Fig. 6. The analogues are effective for treating intracellular pathogen infections, specifically Mycobacterium infections (e.g., M. bovis, M. tuberculosis, etc.). See abstract; see also 0022. The structurally related analogues work by inhibiting the mycobacterium glutamine synthetase (MbGS). One specific effective analogue is phosphinothricin (PPT) having the structure
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. See 0037, last sentence; see also 0039.
While Horowitz teaches that phosphinothricin as an MSO analogue is effective for treating Mycobacterium infection including M. tuberculosis and M. bovis, Horowitz does not expressly teach arsinothricin.
Kuramata found 2 novel compounds produced by bacteria in the rhizospheres of rice plants. One of them, arsinothricin (AST), is an arsenic mimetic of phosphinothricin (PPT). See abstract. It was named arsinothricin due to its similar structure to phosphinothricin. See p. 2nd col. 1st full paragraph.
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. AST was shown to be absorbed by E. coli and possess toxic antibacterial efficacy against it. See abstract. Results suggest that this is because of AST's structural similarity to PPT. See p. 729, 1st paragraph, last sentence.
One of ordinary skill in the art (POSA) would have found it obvious to inhibit the growth of or treat infections caused by M. tuberculosis or M. bovis because Horowitz teaches that MSO analogues such as phosphinothricin (PPT) are effective agents for treating mycobacterium infections such as infections caused by M. tuberculosis or M. bovis while Kuramata teaches that arsinothricin (AST) is an antibacterial analogue and mimetic of PPT. The POSA would have had a reasonable expectation of success in for inhibiting M. tuberculosis or M. bovis because AST is an antibacterial agent that is structurally very close to PPT (
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) and is described as having PPT mimetic activity. Thus, one of ordinary skill in the art would have reasonably believed that AST would, like PPT, possess antibacterial efficacy against infections cause by Mycobacterium.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Regarding Claims 2-4, 10, 18 and 19, Horowitz teaches antimicrobial treatment of M. bovis and M. tuberculosis as outlined above.
Regarding Claim 5, wherein the infections agent does not express Arsinothricin N-acetyltransferase or phosphinothricin N-acetyltransferase. Horowitz does not mention that these transferases are present. Additionally, there is no evidence that each of these transferases are expressed by M. tuberculosis and M. bovis of Horowitz. Lastly, one of ordinary skill in the art would have reasonably expect that arsinothricin would be effective in Mycobacterium that lacks expression of the claimed transferases because the combination of Horowitz and Kuramata suggests the use of AST for treating Mycobacterium.
Regarding Claim 11, comprising administering to the subject arsinothricin or a salt thereof at an effective dose in the range of from about 0.001 to about 100 mg/kg of body weight per day. Horwitz teaches MSO antimicrobial administration to animals at dose amounts of 1.56, 3.13, 6.25, 12.5, 24, 50, 100 mg/kg/day. See Table 2 at p. 5.
B. Claims 6, 8, 12, 14-16, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Horowitz et al. (US 2004/0157802 A1) in view of Kuramata et al. (Environ. Chem. 2016, 13, 723–731 – cited in 9/22/2025 IDS) as applied to Claims 1-5, 10, 11, 18 and 19, taken further in view of De Block et al. (The EMBO Journal 6(9):2513-2518. (1987) – cited in 9/22/2025 IDS).
Claimed invention
Claims 6, 8, 12, 14-16 and 20 each require the infectious agent to express phosphinothricin N-acetyltransferase (PAT) or arsinothricin N-acetyltransferase (AAT).
Prior art
The disclosures for Horwitz and Kuramata are described above. Their combination suggests treatment of infection by using of AST for inhibiting M. tuberculosis or M. bovis. However, their combination does not expressly teach expression of phosphinothricin N-acetyltransferase (PAT) or arsinothricin N-acetyltransferase (AAT).
However, De Block teaches the cloning and characterization of a bialaphos resistance gene (bar) from Streptomyces hygroscopicus that encodes phosphinothricin acetyltransferase (PAT), an enzyme involved in the bialaphos biosynthetic pathway. De Block further discloses that PAT acetylates the free -NH2 group of phosphinothricin (PPT), thereby detoxifying the compound and preventing autotoxicity in the producing organism. (Page 2513, second column, second paragraph.) In view of this teaching, the POSA would have reasonably expected the bacteria expressing PAT would be capable of acetylating other compounds with a free -NH2 group and structural similarity to PPT such as arsinothricin. Accordingly, it would have been obvious to treat bacterial infection by isolating and testing the bacterium to identify whether the infecting bacterium expresses phosphinothricin N-acetyltransferase (PAT), with a reasonable expectation that such expression could impart resistance by acetylation of arsinothricin. The POSA would reasonably seek to inhibit PAT in the expressing bacteria with an inhibitor thereof by combining the inhibitor with PPT treatment as protection against PPT acetylation.
Regarding Claim 14, comprising administering to the subject arsinothricin or a salt thereof in combination with an inhibitor of phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase in unit dosage form containing about 0.05 to about 10000 mg of each of arsinothricin or a salt thereof or the inhibitor of phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase per unit dosage form. Given that treatment of a human is disclosed (see Horwitz, Claim 12), and disclosed dose amounts of 1.56, 3.13, 6.25, 12.5, 24, 50, 100 mg/kg/day (see Table 2 at p. 5), the POSA would have reasonably considered treatment of an average sized human man at ~90 kg with who has an infection. Thus, the POSA would easily calculate the amount based on his weight and arrive at the claimed amount, e.g., 6.25 mg times 90 is 563 mg. The POSA would reasonably understand that the acetyltransferase inhibitor amount may be adjusted to optimize protection of PPT.
Regarding Claim 15, comprising administering to the subject arsinothricin or a salt thereof in combination with an inhibitor of phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase to achieve a peak plasma concentration of from about 0.25 to about 200 μM of each of arsinothricin or a salt thereof or the inhibitor of phosphinothricin N- acetyltransferase or arsinothricin N-acetyltransferase per unit dosage form. Horwitz teaches antimicrobial activity of MSO analogues at concentrations of 10, 20, 100, 200, 1000, 2000 μM. See 0028. The POSA would have reasonably sought to administer AST at amounts to obtain plasma concentrations of the MSO analogue disclosed as providing antimicrobial effect. The POSA would reasonably understand that the acetyltransferase inhibitor amount may be adjusted to optimize protection of PPT. This meets the limitation of Claim 16 wherein the therapeutically useful and effective concentration range of at least about 1 mg/ml of arsinothricin. For example, 10μM of arsinothricin corresponds to 2.2507 mg/ml.
Regarding Claim 20, further comprising isolating the infectious agent, testing the infectious agent for the expression of phosphinothricin N-acetyltransferase and/or arsinothricin N-acetyltransferase, and administering to the subject an inhibitor of phosphinothricin N- acetyltransferase or arsinothricin N-acetyltransferase. As outlined above, it would have been obvious to treat bacterial infection by isolating and testing the bacterium to identify whether the infecting bacterium expresses phosphinothricin N-acetyltransferase (PAT), with a reasonable expectation that such expression could impart resistance by acetylation of arsinothricin.
C. Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Horowitz et al. (US 2004/0157802 A1) in view of Kuramata et al. (Environ. Chem. 2016, 13, 723–731 – cited in 9/22/2025 IDS) as applied to Claims 1-5, 10, 11, 18 and 19, taken further in view of Pohl et al. (US PG-PUB 2005/0214251).
Claimed invention
Claim 17 limits claim 11, further comprising administering arsinothricin via sublingual, vaginal or spinal route.
Prior art
The disclosures for Horwitz and Kuramata are described above. Their combination suggests treatment of infection by using of AST for inhibiting M. tuberculosis or M. bovis. However, their combination does not expressly teach administration sublingually.
However, sublingual administration of drugs was already known for providing therapeutic agents with rapid onset. See Pohl, abstract, 0010. A POSA would have sought to administer AST sublingually in order to achieve faster systemic absorption and therapeutic effect, with a reasonable expectation of success, since sublingual delivery was a predictable and established route for administering drugs.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,298,335 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating an infection in a subject including infection caused by carbapenem-resistant Enterobacter cloacae including those that may or may not express phosphinothricin N-acetyltransferase and/or arsinothricin N-acetyltransferase comprising administering to the subject an effective amount of arsinothricin or a salt thereof. Each claim set further teaches administration of the same inhibitors of phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase with arsinothricin. The administration encompasses oral mucosal delivery.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,303,485 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a method of treating an infection in a subject including infection caused by carbapenem-resistant Enterobacter cloacae including those that may or may not express phosphinothricin N-acetyltransferase and/or arsinothricin N-acetyltransferase comprising administering to the subject an effective amount of arsinothricin or a salt thereof. Each claim set further teaches administration of the same inhibitors of phosphinothricin N-acetyltransferase or arsinothricin N-acetyltransferase with arsinothricin. The administration encompasses oral mucosal delivery.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622